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An interview with Professor Louise Donnelly

Louise Donnelly is professor of respiratory cell biology, within the section of airway disease at the National Heart and Lung Institute at Imperial College London and the respiratory biomedical research unit at Royal Brompton Hospital.

Louise has worked in the field of respiratory cell biology for many years with a particular interest in the cellular profile in inflammatory lung diseases including chronic obstructive pulmonary diseases (COPD).

COPD is an umbrella term to describe lung disease where there is chronic obstruction of lung airflow that is not fully reversible and interferes with normal breathing. It includes 'chronic bronchitis' and 'emphysema'.

We sat down with her to discuss her research into COPD.

1. How and why did you become a research scientist?

I think I was always interested in how things worked and problem-solving. From an early age I liked to be able to go and find things out for myself rather than be told that things worked, which is why I liked doing science at school. I very quickly worked out that I quite liked doing biology and chemistry (I wasn't quite so keen on physics). I went on to do a degree in biochemistry which I loved and then got into animal cell biology, followed by a PhD in cell biology and continued that with a post doc in clinical pharmacology. That got me involved in cell to cell signalling, how pathways worked and how things got switched on and off.

By this point I had reached a place where I wanted to put all this knowledge into practice. I was given the opportunity to come and work with Professor Peter Barnes so I could put some of those cell pathways to a translational concept working with cells from patients and that’s I enjoy doing the most.

Professor Louise Donnelly

2. What research are you doing at the moment and why is it important?

For the last ten years I have been working on chronic obstructive pulmonary disease (COPD) and what I have found is that a lot of people really don’t understand what COPD is and some haven’t even heard of the term and yet it affects over a million people in the UK each year and is the cause of death for about 30,000 people each year.

People may understand when we talk about chronic bronchitis or emphysema and actually COPD is an umbrella term for all of those features but I've been really interested in why people get COPD.

Currently I'm working on the link between cigarette smoking and COPD, as not all smokers go on develop the disease. We've been looking at a particular cell called the macrophage which is a white cell that you find in the lungs. They are a fantastic cell type because when they are working properly they clear and get rid of anything that we inhale, including pollution. They are also fantastic at removing bacteria so they keep your airways nice and clean.

However in patients with COPD we find that there are more of these macrophages which you would think would mean the lungs should be absolutely pristine but in fact they are not. So although there are more macrophages they are not doing their job properly.

Our research group has actually shown that the macrophages in patients with COPD stop eating the bacteria. We also found that not only are the macrophages not eating the bacteria but they are also producing more inflammatory proteins causing inflammation. This means patients then develop chest infections or have exacerbations and there condition worsens.

Our team is looking to find different ways of switching off these macrophages such as looking at new anti-inflammatory treatments and are working with a variety of pharmaceutical companies to see whether we can find new therapies. Some of these potential treatments have gone into clinical trials but have unfortunately been unsuccessful but we continue to look at new treatments. We think it is incredibly important because exacerbations of COPD are one of the main reasons why people go into hospital in the winter months in the UK, so that if we can develop treatments that not only makes the patients better and slows down their cause of disease but also saves money for the NHS.

3. What other areas of research are you looking into?

We’re looking not just at macrophages but the other types of cells you find in the lungs as well including the airway epithelial cells, the layer of cells that line the inside of the lungs, and fibroblasts found inside tissue which make all the matrix that holds the lung together. I've been working on those as well and trying to work out why factors such as bacteria, cigarettes and even pollution can affect these cells causing changes and why they affect some people with the disease but not others.

4. You mentioned that some of the trials have not worked, so what kind of treatments do you think might work for the future and how might these affect patients?

One of the big issues that is out there not just in lung disease but in all kinds of infectious diseases at the moment is antibiotic resistance. If we can somehow activate patients’ normal immune system so that macrophages can remove and eat the bacteria more, it might negate or reduce some of the need for some of the antibiotics.

Or we could develop some novel treatments that make macrophages eat more in conjunction with antibiotics so that you don’t need to use them as long and the chance for resistance is reduced. So what we want to do is to see whether we can screen lots of new drugs using an assay that we have developed using cells from patients with COPD. The aim would be to see if we can screen for new drugs more quickly and then put them forward for testing.

5. What’s next for COPD research in general, internationally, in the UK and for your team?

The tricky thing with COPD is that because it takes such a long time for the disease to develop, so trying to do clinical trials has actually turned out to be incredibly difficult. One of the things we are trying to understand now is what’s causing COPD. We are trying to look at smokers to find out whether people over a long period of time to why some develop COPD and others do not. It’s quite simplistic to say that if you just give up smoking, everything is going to fine. At least 20 per cent of the population are continuing to smoke cigarettes so we are going to have the disease with us for the foreseeable future.

I think within the field of COPD research in general we are beginning to understand how COPD and other diseases work together such as diabetes and cardiovascular disease to affect patients.

Within my research team, we will continue to look specifically at macrophages and epithelial cells to see how they may be working together. As I mentioned earlier it seems to be in COPD that these macrophages are switched on to stop eating (but continue to be really inflammatory) and what we are trying to do is to find ways of switching them back to being a nice, happy macrophage and to see whether that’s possible.

6. And finally, what’s your favourite thing about doing research?

One of the good things about doing research is that you are doing something different every day. But my favourite thing about research is looking at the data and seeing what we have found and seeing what this means. The other thing that I think is fantastic is that over the years we have trained a whole new generation of lung researchers and to be able to enthuse people working in the area of lung research has been fantastic. We have been able to train a number of MSc students and PhD students who have gone on and continued to work in the field and that’s a really good thing to have.

But something that people may not realise in research is that it can take a long time to get an experiment to work, I don’t think people always appreciate that you work really hard for weeks and months and it all goes wrong at the end!